Oxygen free radicals and oxidative damage have been shown to be involved in neurodegenerative diseases including Parkinson's Disease. The PI has discovered that certain nitrone-based free radical traps (NRTs), which react with and trap free radicals, protect experimental animals from an experimental model of Parkinson's Disease, the MPTP (l-methyl-4-phenyl-1,2,5,6- tetrahydropyridine)-induced loss of caudate dopamine in C57BL/6 mice. They have also discovered that MPTP induces increased hydroxyl free radical formation in treated mice. The overall goal of this Phase I proposal is to determine if NRTs protect in experimental models of Parkinson's Disease. The specific aims are: (1) to determine if, during MPTP-induced Parkinson's Disease, the tissue is injured by oxidative damage; (2) to determine the effectiveness of a series of NRTs in preventing brain damage as assessed by dopamine caudate loss and determine if NRTs protect by reacting with either the primary reactive oxygen species (ROS) or their secondary reaction products and thus prevent the oxidative cascade of events which leads to tissue injury; and (3) to synthesize and test NRTs that have potential effectiveness in treating Parkinson's Disease patients.